Li Pingping, Lan Ping, Liu Sheng, Wang Yaochun, Liu Peijun
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
The Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Genet. 2020 Aug 28;11:931. doi: 10.3389/fgene.2020.00931. eCollection 2020.
: The Pals1-associated tight junction (PATJ) is a Crumbs (CRB) complex component that regulates epithelial cell apico-basal polarity and directional migration. This study assessed PATJ expression in clear cell renal cell carcinoma (ccRCC) vs. normal tissues and associated with ccRCC progression and prognosis. : The effects of PATJ knockdown were investigated on regulation of normal kidney epithelial cell viability and protein expression . The mRNA data in ccRCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and analyzed with UALCAN, LinkedOmics, Kaplan-Meier Plotter, GEPIA, and SurvExpress tools. Immunohistochemistry was performed for PATJ in tissue microarray sections ( = 150 ccRCC and 30 normal renal specimens). Normal human kidney tubular epithelial cell (HKC) cells were transfected with and negative control siRNA for cell viability CCK-8 assay, flow cytometry, and western blots. : The data showed that mRNA and protein were downregulated in ccRCC tissues and cell lines. Downregulation of mRNA was associated with male patients, advanced tumor stages, grades, and ccB subtypes as well as poorer overall and disease-free survival of patients. Furthermore, PATJ protein was also significantly downregulated in ccRCC tissues and associated with advanced tumor pathologic, TNM stages and poorer overall. , knockdown of PATJ expression promoted HKC proliferation and the activation of mitogen-activated protein kinases (MAPK) pathway proteins. : This study revealed that a decrease of PATJ in ccRCC, which was associated with male patients, advanced tumor, and poorer survival, suggesting that PATJ may be a useful prognostic biomarker and therapeutic target for ccRCC.
Pals1相关紧密连接蛋白（PATJ）是一种Crumbs（CRB）复合体成分，可调节上皮细胞的顶-基极性和定向迁移。本研究评估了PATJ在透明细胞肾细胞癌（ccRCC）与正常组织中的表达情况，并探讨其与ccRCC进展和预后的关系。研究了PATJ基因敲低对正常肾上皮细胞活力和蛋白表达调控的影响。ccRCC中的mRNA数据来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO），并使用UALCAN、LinkedOmics、Kaplan-Meier Plotter、GEPIA和SurvExpress工具进行分析。对组织微阵列切片（150例ccRCC和30例正常肾标本）进行PATJ免疫组化检测。将人正常肾小管上皮细胞（HKC）用PATJ和阴性对照小干扰RNA转染，进行细胞活力CCK-8检测、流式细胞术和蛋白质印迹分析。数据显示，ccRCC组织和细胞系中PATJ mRNA和蛋白表达下调。PATJ mRNA下调与男性患者、肿瘤晚期、高级别及ccB亚型相关，且患者的总生存期和无病生存期较差。此外，ccRCC组织中PATJ蛋白也显著下调，并与肿瘤病理分期、TNM分期及较差的总生存期相关。PATJ表达敲低促进了HKC增殖及丝裂原活化蛋白激酶（MAPK）信号通路蛋白的激活。本研究表明，ccRCC中PATJ表达降低与男性患者、晚期肿瘤及较差的生存率相关，提示PATJ可能是ccRCC有用的预后生物标志物和治疗靶点。
